Biology Reference
In-Depth Information
al., 2004). Therefore, adaptations in downstream circuitry, such NAc and PFC, are likely to
be more important for the longer lasting behavioral changes associated with drug addiction.
As discussed below, the critical neuroplastic changes responsible for sensitization would shift
from its initiation site in the VTA to its sites of expression in other brain regions, such as the
NAc (Wolf, 1998; Vanderschuren and Kalivas, 2000).
Figure 4. Involvement of NMDA and AMPA receptors in the induction of LTP. A: Potentiation of
AMPAR/NMDAR after multiple injections is attributed to an increase of AMPA currents. B: Multiple
injections of cocaine were found to increase the AMPAR/NMDAR ratio at 5 but not at 10 days after
cocaine administration. (Source: Adapted from Borgland et al., 2004).
The above-mentioned studies have linked glutamate induced neuroplasticity in the VTA
with the locomotor effects of cocaine. To study the neurochemical background of reward
related learning it is possible to use a conditioned place preference to cocaine paradigm
(CPP). This approach is different from the model of behavioral sensitization that uses
repeated cocaine adminstration. CPP is based on operant behavior controlled by cue stimuli.
CPP consists of two distinct compartments or chambers, one of them with a grid floor and
black walls, and the other with a mesh floor and black and white striped walls. As a general
procedure, rodents are allowed to freely explore both compartments and receive cocaine
(usually intracerebral microinjections) only in one of the two compartments, so that the
rodents are able to associate one of the compartments with cocaine effects. At the end of the
experiment, the rodents undergo a preference test. The amount of time spend in each chamber
is recorded as a measure of the rewarding effects of cocaine.
Using CPP, Harris and Aston-Jones (2003) explored the effects of glutamate release in
the VTA. Rodents were first allowed to associate one of the two compartments with cocaine.
